Pure heart rate reduction: the If channels from discovery to therapeutic target

Studies indicate that increased heart rate is a risk factor for ischaematic cardiac events; accordingly heart rate reduction may improve outcome. Beta blockers and some calcium channel blockers reduce heart rate but their use may be limited by negative inotropic effects and several contraindications. Ivabradine, a selective sinus node If channel inhibitor, represents a therapeutic innovation in the treatment of ischaemia. Preclinical and early clinical studies show that ivabradine can reduce heart rate without affecting cardiac systolic function, suggesting that If inhibition may be an effective approach to minimise both angina and the underlying ischaemia. In clinical studies ivabradine has anti-anginal and anti-ischaemic effects in patients with stable angina and has comparable efficacy to atenolol and amlodipine. This anti-ischaemic effect is also observed in elderly patients in whom there is a greater incidence of stable angina. Furthermore, the absence of additional cardiac effects associated with If inhibition suggest that this approach may be effective in other patient groups, such as those at risk of acute coronary events or compromised left ventricular function. Further clinical trials with ivabradine to evaluate fully the therapeutic potential of If inhibition are ongoing.